The pathogenecity of certain Lactobacillus strains has been reported in 1938 [F. Marshall: Der Döderleinische Bacillus vaginalis als Endokarditiserreger, Zentr. Bact. Parasit. Kde. I. Abt. Orig., 141:153-159 (1938); E. Biocca és A. Sepilli: Human infections caused by lactobacilli, J. Inf. Dis., 81:112-115 (1947); W. Sims: A pathogenic Lactobacillus, J. Path. Bact., 87:99-105 (1964); B. Rosan and B. F. Hammond: Toxicity of Lactobacillus casei, J. Dent. Res., 44:783-787 (1965); M. E. Sharpe, L. R. Hill and S. P. Lapage: Pathogenic lactobacilli, J. Med. Microbiol., 6, 281-286 (1973).
G. Wied reported in 1952 [ ZbI. Bact., 160:413 (1952)] that certain Lactobacillus strains show mucous membrane damaging activity. Rosan and Hammond [1965, ibid.] reported that, with Lactobacillus strains strongly pathogenic to mice, intradermal inoculation of bacteria both in living and in thermally inactivated states causes necrosis on the back of rabbits.
K. Újhelyi has found that necrosis can be induced also by Lactobacillus strains cultivated from vagina. Based on his observation, it can be stated that the body of the bacterium contains a toxin which is responsible for damaging the epithelia [Újhelyi K. et al.: Role of Lactobacillus in urogenital inflammations and their treatment with vaccination, Symposium cum participatione internationalis de Biocenosi Vaginae, Smolenie, 1983]. Certain strains, injected intradermally to the back of rabbits, cause necrosis of smaller or larger areas, while others cause necrosis only in higher concentration or do not cause necrosis at all. K. Újhelyi has found that rabbits can be immunized by vaccination against the necrotic effect. He vaccinated rabbits intramuscularly with vaccine produced from certain Lactobacillus strains. Six weeks later, he intradermally administered cell-suspensions prepared from strains that have been shown previously to be necrotic, and observed that necrosis was not caused or was only caused in a lesser degree than in the case of non-vaccinated rabbits.
Furthermore, K. Újhelyi has found that Trichomonas vaginalis contributes to the rise in vaginal pH by consuming lactic acid produced by Lactobacillus strains in the vagina, thereby promoting the over-proliferation of Lactobacillus strains. Consequently toxin is present in higher concentration which, by damaging the mucous membrane, causes cell necrosis.
Furthermore, it is known that Lactobacillus strains, because of their receptor inhibiting and antibiotic activity as well as pH-modifying effect, are antagonistic to pyogenic microorganisms [Reddy et al.: Natural antibiotic activity of Lactobacillus, Dairy Prod. J. 18:15-22 (1983); Salminen et al.: Lactic acid bacteria in the gut in normal and disordered states, Dig. Dis., 10:227-238 (1992)].
Recently, it has been shown that Lactobacillus strains can bind directly to T-lymhocytes since both the T-helper and T-killer cells have specific receptors for Lactobacillus strains. Furthermore, Lactobacillus strains promote the gamma-interferon production of the lymphocytes and the cytotoxic activity of the natural killer cells [De Simone C., et al.: Enhancement of immune response of murine Peyer's pothes by a diet supplemented with yoghurt, J. Immunopharmacol., 1:87-95 (1987)]. It has been shown that Lactobacillus strains aspecifically increase the production of IgM and IgG [Blocksma et al.: Adjuvant activity of lactobacilli, different effects of viable and killed bacteria, Clin. Exp. Immunol., 37:367-373]. Additionally, under experimental conditions, Lactobacillus strains show antitumour and macrophage-activating activity [Kato I. et al.,: Antitumor activity of Lactobacillus casei in mice, Gann, 72:517-523 (1983); Oda M. et al.: Antitumor polysaccharide from Lactobacillus sp., Agric Biol. Chem., 47:1623-1627 (1983)]. H. Rüttgers has found that immunostimulation by Lactobacillus strains causes a significant long-lasting rise in secretory immunoglobulin level in the vagina [Bacterial vaginitis: Protection against infection and secretory immunoglobulin levels in the vagina after immunization therapy with Gynatren, Gynecol. Obstet Invest, 26:240-249 (1988)].
Újhelyi of al. [1983, ibid.] used parenterally administered Lactobacillus strains for aspecific immunostimulation and observed that the Lactobacillus strains used, in contrast to other aspecific immunostimulation (e.g. by BCG, endotoxins etc.), show protective effect against certain bacterial toxins. This applies especially to toxic Lactobacillus strains.
In trials carried out with vaccines (Gynevac®, Gynatren®, Solco Trichovac®) made of strains cultured by Újhelyi it has been demonstrated that immunostimulation by Lactobacillus strains, in contrast to other therapeutic treatments, restores the biological balance of the vagina, normalizes the pH, decreases the number of pathogenic bacteria, and contributes to the propagation of Döderlein-flora (a mixed population of Lactobacillus strains capable of being cultivated from vaginal specimens). It is an accepted fact that inflammatory diseases of the vagina caused by bacterial and Trichomonas infections can be cured in this way more successfully than by other therapy and that such inflammatory conditions are a major cause of premature births. Therefore, the frequency of premature births can also be decreased by such therapy [see e.g. in Genitalinfektion der Frau (SolcoTrichovac/Gynatren), Geburtsch. u. Frauenheilk, 44:311 (1984); E. Lázár, Gy. Varga, I. Institoris and K. Újhelyi: Investigating the factors, especially vaccination with lactobacilli, influencing the premature births, in Kazincbarcika (in Hungarian), Magyar Nöorvosok Lapja (Journal of Hungarian Gynaecologists), 51:353-356 (1986); E. Lázár, Gy. Varga, I. Institoris and K. Újhelyi: Decreasing the ratio of neonates with small weight by lactobact vaccination of pregnant women (in Hungarian), Orvosi Hetilap (Physicians Weekly), 37:2263-2268 (1981), Rüttgers, 1988, ibid., K. Újhelyi, Gy. Philipp, Gy. Plank and V. Sági: The Trichomonas syndrome I (in Hungarian), Magyar Nöorvosok Lapja (Journal of Hungarian Gynaecologists), 36:433-442 (1973); Sharon et al., New England Journal, Dec. 28, 1995.].
More than 50% of men aged 50 or more suffer from prostate hyperplasia and/or prostate inflammation. In spite of numerous known and utilized therapies, treatment is often unsuccessful. Taking into consideration the known and generally accepted pathogenesis, it could not be supposed that such diseases can be healed with vaccines comprising Lactobacillus strains successfully.
The inventors of the present invention have, however, found that conditions in the prostate are favorable to the proliferation of Lactobacillus strains and that pathogenic lactobacilli can often be cultivated from patients suffering from chronic prostate inflammation and/or prostate hyperplasia. On this basis, therapeutic utilization of vaccines comprising Lactobacillus strains for treating such patients has been achieved.